Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Aplasia cutis congenita in monozygotic twins.

Aplasia cutis congenita (ACC) is defined as complete or partial loss or absence of skin at birth and it can occur on any part of the body, but most commonly on the scalp. Single offspring with ACC have been reported in most case reports, but cases in twins are rarely reported. Here, we report two cases of ACC, monozygotic twin boys presented with scattered skin absence over the scalp vertex after birth. All the lesions presented as ulcers with no hair and healed with scars, otherwise, the twins were well developed mentally and physically. In addition, the whole exome sequencing of the twins and their parents might provide diagnosis and classification assistance.

Clinical outcomes of the cuff wrapping technique in the modified Bentall procedure: a propensity score-matched study.

Background: This study was designed to evaluate the clinical outcomes of our modified cuff wrapping Bentall (M-Bentall) procedure, which uses a cuff wrapping technique with remnant aortic root tissue. Methods: From July 2017 to December 2021, a total of 136 patients met the inclusion criteria for this study. Among them, patients who underwent the modified Bentall procedure using the cuff wrapping technique were included in the M-Bentall group (n=46), while patients who underwent the classic Bentall (C-Bentall) procedure were categorized into the C-Bentall group (n=90). To reduce baseline differences between the two groups, 1:1 nearest-neighbor propensity score matching (PSM) was performed. Demographic and perioperative data were documented and compared between the two groups. Results: Ninety patients were successfully matched (45 pairs). In-hospital mortality was not significantly different between the two groups after PSM (P=1). No differences were found in serious adverse events. The cardiopulmonary bypass (CPB) time was longer in the M-Bentall group than in the C-Bentall group (154 vs. 126 min, P=0.018). The same was also observed for the aortic cross-clamp time (113 vs. 92 min, P=0.009). Postoperatively, the peak value of D-dimer showed a significant difference, with higher values in the C-Bentall group (4.73 vs. 2.89 mg/L, P=0.019). The incidence of postoperative contrast extravasation at the aortic root (P=0.030) was higher in the C-Bentall group. The incidence of persistent aortic-right atrial shunts showed an increased tendency in the C-Bentall group (8.89% vs. 0%, P=0.117). Conclusions: The cuff wrapping technique is a safe and effective method to facilitate hemostasis of the aortic root in the modified Bentall procedure.

Diclazuril-induced expression of CDK-related kinase 2 in the second-generation merozoites of Eimeria tenella.

Diclazuril is a classic anticoccidial drug. The key molecules of diclazuril in anticoccidial action allows target screening for the development of anticoccidial drugs. Cyclin-dependent kinases (CDK) are prominent target proteins in apicomplexan parasites. In this study, a diclazuril anticoccidiosis animal model was established, and the transcription and translation levels of the CDK-related kinase 2 of Eimeria tenella (EtCRK2) were detected. mRNA and protein expression levels of EtCRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localised in the cytoplasm of the merozoites. The fluorescence intensity of EtCRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group. The anticoccidial drug diclazuril against E.tenella affects the expression pattern of EtCRK2 molecule, and EtCRK2 is a potential target for new drug development.

Evaluation of aristolochic acid Ι nephrotoxicity in mice via 1H NMR quantitative metabolomics and network pharmacology approaches.

Background: Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent. Methods and results: Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline. Conclusion: This work provides a meaningful insight for the mechanism of AAΙ renal injury.

Correlative increasing expressions of KIF5b and Nav1.7 in DRG neurons of rats under neuropathic pain conditions.

Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain.

Surgical treatment of thoracic aortic pseudoaneurysm caused by Brucella melitensis.

Thoracic aortic pseudoaneurysm caused by Brucella melitensis is extremely rare with extremely few cases reported to date. Herein, we present the case of a 65 year-old man with a huge pseudoaneurysm of the proximal descending thoracic aorta, involving the left subclavian artery and distal arch. Surgery was performed to replace the proximal descending aorta with a self-made bovine pericardial duct and the left subclavian artery with a 10 mm artificial vessel under deep hypothermic circulatory arrest; the patient recovered uneventfully. However, continued follow-up is required for long-term results.

Molybdenum-Induced Apoptosis of Splenocytes and Thymocytes and Changes of Peripheral Blood in Sheep.

To investigate the effects of molybdenum (Mo) on apoptosis of lymphocytes and changes of peripheral blood in sheep, a total of 20 5-month-old healthy female sheep were randomly divided into five groups of 4 and orally administered with water containing Na2MoO4·2H2O (0, 5, 10, 20, and 50 mg/kg BW/day) for 28 days. Jugular vein blood was taken on the 0th, 7th, 14th, 21st, and 28th day of Mo treatment, respectively. On the 28th day, the spleen and thymus were removed for observing histopathology and apoptosis-related DNA damage by hematoxylin and eosin (HE) staining and TdT­mediated dUTP Nick-End Labeling (TUNEL) staining, respectively. The blood routine indexes were determined by an automatic blood analyzer. Further, the apoptosis of lymphocytes and changes in mitochondrial membrane potential (MMP) of peripheral blood were analyzed by flow cytometry. Results showed that excessive Mo induced apoptosis-related DNA damage in the splenocytes and thymocytes and significantly increased the apoptosis indexes of the splenocytes and thymocytes (P < 0.01). Furthermore, the treatment with excessive Mo significantly decreased the MMP (P < 0.01) and promoted apoptosis in peripheral blood lymphocytes (P < 0.01). And the number of WBC, Lymph, Gran, and RBC and the indexes of HGB and HCT were also significantly decreased (P < 0.05 or P < 0.01), while RDW was significantly increased by excessive Mo (P < 0.05 or P < 0.01). In conclusion, excessive Mo-induced DNA damage and apoptosis of the lymphocytes changed the RBC-related indexes of the peripheral blood in sheep.

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA's metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.

Constituents from Chloranthus multistachys and their cytotoxic activities against various human cancer cell lines.

Two new furanoeremophilane sesquiterpenoids, namely, 6,9-dioxo-1α,4α-dihydroxy-furanoeremophilane (1) and 4α,5α-epoxy-6,9-dioxo-1α-hydroxyl-furanoeremophilane (2), and 10 known compounds were isolated from the whole plant of Chloranthus multistachys, and compound 3 was converted to derivative 3a. Their structures were determined based on extensive spectroscopic analysis. All compounds were evaluated by using five cancer cell lines: PC3, LNcap, A549, K562, and HEL. The derivative 3a exhibited excellent cytotoxic activities, with the IC50 against HEL cells being the lowest at 1.322 ± 0.08 µM, which was comparable to that of the positive control (doxorubicin). Mechanism studies showed that the anticancer activity of 3a may be associated with cell cycle regulation.

Flanged Bentall Plus Cabrol Procedure for Interventricular Septal Dissection in Behçet's Disease.

Behçet's disease with interventricular septal dissection is extremely rare, and its surgical treatment is even more challenging. One such treatment with interventricular septal dissection repair was followed by the flanged Bentall and Cabrol techniques. The flange of the flanged composite graft was attached to the left ventricular outflow tract instead of the fragile annulus. The Cabrol procedure was performed to reduce anastomotic tension at the coronary button sites. Good short-term results were achieved.

Morphological investigations of endomorphin-2 and spinoparabrachial projection neurons in the spinal dorsal horn of the rat.

It has been proved that endomorphin-2 (EM2) produced obvious analgesic effects in the spinal dorsal horn (SDH), which existed in our human bodies with remarkable affinity and selectivity for the µ-opioid receptor (MOR). Our previous study has demonstrated that EM2 made synapses with the spinoparabrachial projection neurons (PNs) in the SDH and inhibited their activities by reducing presynaptic glutamate release. However, the morphological features of EM2 and the spinoparabrachial PNs in the SDH have not been completely investigated. Here, we examined the morphological features of EM2 and the spinoparabrachial PNs by using triple fluorescence and electron microscopic immunohistochemistry. EM2-immunoreactive (-ir) afferents directly contacted with the spinoparabrachial PNs in lamina I of the SDH. Immunoelectron microscopy (IEM) were used to confirm that these contacts were synaptic connections. It was also observed that EM2-ir axon terminals contacting with spinoparabrachial PNs in lamina I contained MOR, substance P (SP) and vesicular glutamate transporter 2 (VGLUT2). In lamina II, MOR-ir neurons were observed to receive direct contacts from EM2-ir varicosities. The synaptic connections among EM2, MOR, SP, VGLUT2, and the spinoparabrachial PNs were also confirmed by IEM. In sum, our results supply morphological evidences for the analgesic effects of EM2 on the spinoparabrachial PNs in the SDH.

Solitary splenic tuberculosis: A case report.

BACKGROUND: Solitary splenic tuberculosis (TB) is unusual and rarely reported. Whether splenic TB is best treated surgically is still controversial. We describe a 73-year-old man with solitary splenic TB and no extrapulmonary TB. CASE SUMMARY: We report the case of a 73-year-old man with solitary splenic TB who complained of emaciation and fatigue. Abdominal computed tomography (CT) images suggested a splenic space-occupying lesion. We then performed a CT-guided splenic biopsy. The postoperative pathological examination revealed splenic TB. The patient took quadruple anti-TB medication. After 1 year, the patient recovered his normal weight and had no feeling of fatigue, and the splenic lesion had shrunk significantly. CONCLUSION: If patients receive combined, appropriate, regular, full-time anti-TB treatment, solitary splenic TB may be cured.

Various BDNF administrations attenuate SPS-induced anxiety-like behaviors.

Post-traumatic stress disorder (PTSD) has become epidemic following severely stressful incidents. Previous studies have shown that brain-derived neurotrophic factor (BDNF) has anxiolytic effects on various anxiety or depression disorders including PTSD. However, the detailed mechanisms of BDNF for treating PTSD were rarely investigated. In the current study, single-prolonged stress (SPS) was used as an animal model recapitulating specific aspects for a PTSD-like phenotype. The effects of BDNF on SPS-induced anxiety-like behaviors were investigated. We showed that the levels of BDNF in the cerebro-spinal fluid (CSF) were significantly reduced after the rats experienced SPS. The SPS-induced reductions of percentages of time spent in the central area to total time in the open field test, were dose-dependently mitigated after BDNF intracerebroventricular (i.c.v.) injections. BDNF i.c.v. administration also dose-dependently increased the preference of the light box in the light-dark box test. Both expressions of tyrosine kinase receptor B (TrkB) protein and mRNA in the prefrontal cortex (PFC) and amygdala were significantly increased after SPS challenges. BDNF i.c.v. administration attenuated these compensatory increases of TrkB. At last, the anxiolytic effects of BDNF on SPS model were also observed by using other two injection methods. These results inspired us to study that different administrations of BDNF were used in patients with PTSD in the future, in-depthly.

Left axillary cannulation for acute type A aortic dissection.

The most commonly used arterial cannulation sites for type A aortic dissection are right axillary artery, femoral artery and both. Direct central aortic cannulation has also been reported. In rare cases, it is extremely difficult to choose an arterial cannulation site for type A aortic dissection due to involvement of the right axillary and both femoral arteries. Herein, we present a 39-year-old male with acute type A aortic dissection with involvement of the right axillary and both femoral arteries. Left axillary cannulation was made and selective cerebral perfusion was performed through direct left common carotid artery cannulation during circulatory arrest. Surgery was performed to replace the ascending aorta and total arch combined with a frozen elephant trunk implantation. The patient recovered uneventfully. To our knowledge, this is a rare case of total aortic arch replacement with frozen elephant trunk implantation through left axillary arterial cannulation for type A aortic dissection in the literature. Left axillary cannulation is a safe and useful choice for type A aortic dissection surgery when right axillary and femoral cannulation are not safe and reliable.

Urinary metabonomics study of anti-depressive mechanisms of Millettia speciosa Champ on rats with chronic unpredictable mild stress-induced depression.

As a traditional Chinese medicine (TCM), Millettia speciosa Champ (MSC), exerts a wide range of pharmacological activities. Our research group previously found that MSC has antidepressant effects, but the specific antidepressant mechanisms remain unclear. Therefore, in this study, urine metabolomics based on ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) combined with pharmacodynamics was used to explore the pathogenesis of depression and the antidepressant effects of MSC. The results showed that MSC treatment could significantly improve chronic unpredictable mild stress (CUMS)-induced depression. Urine metabolic showed that the profiles of the CUMS model group were significantly separated from the control group, while the drug-treated groups were closer to the control group, especially the MSC group treated with a 14 g/kg dose of MSC. Furthermore, 9 metabolites, including glutaric acid, L-isoleucine, L-Dopa, sebacic acid, 3-methylhistidine, allantoin, caprylic acid, tryptophol, and 2-phenylethanol glucuronide, were identified as potential biomarkers of depression. Metabolic pathway analysis showed that these potential biomarkers were mainly involved in valine, leucine, and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine degradation, tyrosine metabolism, histidine metabolism, fatty acid biosynthesis, and pentose and glucuronate interconversions. Through Receiver operating characteristic (ROC) analysis and Pearson correlation analysis, the combination of L-isoleucine, sebacic acid, and allantoin, were further screened out as potential pharmacodynamic biomarkers associated with the efficacy of MSC. This study suggests that the integration of metabolomics with pharmacodynamics helps to further understand the pathogenesis of depression and provides novel insight into the efficacy of TCM.

Antiprostate Cancer Activity of Ineupatolide Isolated from Carpesium cernuum L.

OBJECTIVE: The aim of the study was to investigate the antiprostate cancer effects and mechanism of ineupatolide (T-21), a natural product isolated from the Compositae plant Carpesium cernuum L., on PC-3 human prostate cancer cells. METHODS: The effect of T-21 on the proliferation of PC-3 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell migration, and invasion experiments; the morphology of cell apoptosis was observed by Hoechst-propidium iodide staining; the effects of T-21 on PC-3 cell apoptosis and the cell cycle were evaluated by flow cytometry; and the effect of T-21 on the expression levels of phosphorylated protein kinase B (p-AKT), AKT, X-linked inhibitor of apoptosis protein (xlAP), procaspase-3, and poly (ADP-ribose) polymerase (PARP) in PC-3 cells was measured by western blotting. RESULTS: T-21 significantly inhibited the proliferation of cells, and its half-maximal inhibitory concentrations at 12, 24, and 48 h were 38.46 ± 1.01, 24.63 ± 0.70, and 7.36 ± 0.58 µM, respectively. T-21 may promote cell apoptosis in a concentration-dependent manner and block the cell cycle in the G2 and S phases. In addition, T-21 significantly reduced the protein expression levels of p-AKT, AKT, xlAP, procaspase-3, and PARP. CONCLUSION: T-21 exhibits antiproliferation effects on PC-3 cells by promoting apoptosis and arresting the cell cycle in the G2 and S phases. The possible mechanism underlying its potential therapeutic effects against prostate cancer is related to the AKT/xlAP pathway.

Characteristics of organ cysts and their association with type A aortic dissection.

OBJECTIVE: We aimed to evaluate the incidence of organ cysts in patients with type A aortic dissection (TAAD) to assess the association between organ cysts and TAAD. METHODS: Between January 2018 and December 2018, all patients with TAAD undergoing aortic surgery at our center were enrolled into the study; patients undergoing isolated coronary artery bypass grafting at our center were selected as the control group. Baseline differences between the 2 groups were adjusted using propensity-score matching. The incidence of organ cysts was compared between the 2 groups in total and matched cohorts. RESULTS: We enrolled 290 patients with TAAD and 293 patients with coronary artery disease (control group). The incidence of all organ cysts, liver cysts, renal cysts, and other organ cysts, was significantly higher in the TAAD group than in the control group (50.0% vs. 35.5%, p<0.001; 24.5% vs. 10.2%, p<0.001; 33.4% vs. 24.9%, p=0.023; and 6.2% vs. 1.5%, p=0.005; respectively). Among the 191 propensity score-matched patient pairs, the incidence of organ cysts, liver cysts, renal cysts, and other organ cysts was also significantly higher in the TAAD group than in the control group (57.6% vs. 30.9%, p<0.001; 28.8% vs. 11.0%, p<0.001; 39.3% vs. 19.9%, p<0.001; and 8.4% vs. 1.0%, p=0.001; respectively). The incidence of cysts with single-organ and multiple-organ involvement was also significantly higher in the TAAD group than in the control group (34.0% vs. 20.4%, p=0.003; and 23.6% vs. 10.5%, p=0.001). CONCLUSION: Our results show a higher incidence of organ cysts in patients with TAAD which is indicative of a common pathogenetic pathway between organ cysts and aortic dissection.